Bio

Bio

Dr. Venkatasubramanian is a board certified neurologist, vascular neurologist and neurocriticial care physician. She completed her residency training in internal medicine from India and neurology residency and stroke/neurocritical care fellowships at Stanford University Medical Center. She holds a Masters degree in Clinical Trials from University of London. She has been on faculty since 2007. Her primary focus is the clinical care of neurologically critically ill patients in the intensive care unit and patients with acute stroke and TIA in the inpatient stroke unit. In addition, she sees patients with stroke and neurovascular diseases in her stroke clinic as well as patients discharged from the neurological ICU. Her main interests are in brain hemorrhage, unusual and rare causes of stroke, cerebral venous thrombosis and anticoagulation management after strokes.Her research focuses on the study of brain edema and tissue perfusion in intracerebral hemorrhage using novel MRI techniques and biomarkers. She is the Stanford prinicipal investigator for several clinical trials in intracerebral hemorrhage. She is happily married and has two young boys. She enjoys cooking, yoga and coaching her son for spelling and geography bees.

Links

Research & Scholarship

Current Research and Scholarly Interests

I care for neurologically critically ill patients in the intensive care unit and patients with acute stroke and TIA in the inpatient stroke unit. I also see outpatients in a stroke clinic and conduct follow-up of patients discharged from the neurological ICU, in the Outcomes clinic.I am interested in the study of the radiological characteristics and temporal profile of edema/ tissue injury in the perihematomal area around spontaneous intracerebral hemorrhage. I am also interested in developing protocols for emergent reversal of anticoagulation in a life-threatening hemorrhage situation.

Clinical Trials

The purpose of the study is to determine whether desmoteplase is effective and safe in the
treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset
of stroke symptoms.

Transient ischemic attack (TIA) is a transient neurological deficit (speech disturbance,
weakness…), caused by temporary occlusion of a brain vessel by a blood clot that leaves no
lasting effect.
TIA diagnosis can be challenging and an expert stroke evaluation combined with magnetic
resonance imaging (MRI) could improve the diagnosis accuracy.
The risk of a debilitating stroke can be as high as 5% during the first 72 hrs after TIA.
TIA characteristics (duration, type of symptoms, age of the patient), the presence of a
significant narrowing of the neck vessels responsible for the patient's symptoms
(symptomatic stenosis), and an abnormal MRI are associated with an increased risk of stroke.
An emergent evaluation and treatment of TIA patients by a stroke specialist could reduce the
risk of stroke to 2%.
Stanford has implemented an expedited triage pathway for TIA patients combining a clinical
evaluation by a stroke neurologist, an acute MRI of the brain and the vessels and a sampling
of biomarkers (Lp-PLA2). The investigators are investigating the yield of this unique
approach to improve TIA diagnosis, prognosis and secondary stroke prevention. The objective
of this prospective cohort study is to determine which factors will help the physician to
confirm the diagnosis of TIA and to define the risk of stroke after a TIA.

The main purpose of this study is to determine whether treatment with deferoxamine mesylate
is of sufficient promise to improve outcome before pursuing a larger clinical trial to
examine its effectiveness as a treatment for brain hemorrhage.

The overall objective of this Phase III clinical trial is to obtain information from a
population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of
current clinical practice and national demographics of ICH regarding the benefit (or lack
thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS).
This application requests funding for five years to initiate a Phase III randomized clinical
trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The
investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue
plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+
placebo in the management and treatment of subjects with small intracerebral hemorrhage
(ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of
the 3rd or 4th ventricles by intraventricular blood clot).

The purpose of this pivotal study is to demonstrate safety and efficacy of transcranial
laser therapy (TLT) with the NeuroThera® Laser System in the treatment of subjects diagnosed
with acute ischemic stroke. The initiation of the TLT procedure must be feasible for each
subject between 4.5 and 24 hours of stroke onset.

Stanford is currently not accepting patients for this trial.For more information, please contact Stephanie Kemp, (650) 723 - 4481.

The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project
(CRISP) is to develop a practical tool to identify acute stroke patients who are likely to
benefit from endovascular therapy.
The project has two main parts. During the first part, the investigators propose to develop
a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will
generate brain maps of the ischemic core and penumbra. There will be no patient enrollment
in part one of this project.
During the second part, the investigators aim to demonstrate that physicians in the
emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can
accurately predict response to recanalization in stroke patients undergoing
revascularization. To achieve this aim the investigators will conduct a prospective cohort
study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular
therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital,
University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will
have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late
follow-up MRI scan at day 5 to determine the final infarct.

Stanford is currently not accepting patients for this trial.For more information, please contact Stephanie M Kemp, BS, 650-723-4481.

Progesterone for the Treatment of Traumatic Brain Injury IIINot Recruiting

The ProTECT study will determine if intravenous (IV) progesterone (started within 4 hours of
injury and given for a total of 96 hours), is more effective than placebo for treating
victims of moderate to severe acute traumatic brain injury.

Stanford is currently not accepting patients for this trial.For more information, please contact Rosen Mann, (650) 721 - 2645.

Abstract

In comatose post-cardiac arrest patients, a serum neuron-specific enolase (NSE) level of >33 μg/L within 72 h was identified as a reliable marker for poor outcome in a large Dutch study (PROPAC), and this level was subsequently adopted in an American Academy of Neurology practice parameter. Later studies reported that NSE >33 μg/L is not a reliable predictor of poor prognosis. To test whether different clinical laboratories contribute to this variability, we compared NSE levels from the laboratory used in the PROPAC study (DLM-Nijmegen) with those of our hospital's laboratory (ARUP) using paired blood samples.We prospectively enrolled cardiac arrest patients who remained comatose after resuscitation. During the first 3 days, paired blood samples for serum NSE were drawn at a median of 10 min apart. After standard preparation for each lab, one sample was sent to ARUP laboratories and the other to DLM-Nijmegen.Fifty-four paired serum samples from 33 patients were included. Although the serum NSE measurements correlated well between laboratories (R = 0.91), the results from ARUP were approximately 30 % lower than those from DLM-Nijmegen. Therapeutic hypothermia did not affect this relationship. Two patients had favorable outcomes after hypothermia despite NSE levels measured by DLM-Nijmegen as >33 μg/L.Absolute serum NSE levels of comatose cardiac arrest patients differ between laboratories. Any specific absolute cut-off levels proposed to prognosticate poor outcome should not be used without detailed data on how neurologic outcomes correspond to a particular laboratory's method, and even then only in conjunction with other prognostic variables.

Abstract

The purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST-WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging.Consecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST-WD on diffusion-weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor-NIHSS. Twenty-seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST-WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST-WD changes evolved into T2-hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST-WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor-NIHSS (5 versus 1, P=0.001) at 3 months.Wallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST-WD is associated with poor motor and functional recovery after ICH.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is associated with blood-brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage.Twenty-five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (K(trans)) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror-image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher K(trans) values than small hematomas (P<0.005). K(trans) values of lobar hemorrhages were significantly higher than the K(trans) values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher K(trans) values were associated with larger edema volumes.BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

Abstract

Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.

Abstract

Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

Abstract

knowledge on the natural history and clinical impact of perihematomal edema (PHE) associated with intracerebral hemorrhage is limited. We aimed to define the time course, predictors, and clinical significance of PHE measured by serial magnetic resonance imaging.patients with primary supratentorial intracerebral hemorrhage ? 5 cm(3) underwent serial MRIs at prespecified intervals during the first month. Hematoma (H(v)) and PHE (E(v)) volumes were measured on fluid-attenuated inversion recovery images. Relative PHE was defined as E(v)/H(v). Neurologic assessments were performed at admission and with each MRI. Barthel Index, modified Rankin scale, and extended Glasgow Outcome scale scores were assigned at 3 months.twenty-seven patients with 88 MRIs were prospectively included. Median H(v) and E(v) on the first MRI were 39 and 46 cm(3), respectively. Median peak absolute E(v) was 88 cm(3). Larger hematomas produced a larger absolute E(v) (r(2)=0.6) and a smaller relative PHE (r(2)=0.7). Edema volume growth was fastest in the first 2 days but continued until 12 ± 3 days. In multivariate analysis, a higher admission hematocrit was associated with a greater delay in peak PHE (P=0.06). Higher admission partial thromboplastin time was associated with higher peak rPHE (P=0.02). Edema volume growth was correlated with a decline in neurologic status at 48 hours (81 vs 43 cm(3), P=0.03) but not with 3-month functional outcome.PHE volume measured by MRI increases most rapidly in the first 2 days after symptom onset and peaks toward the end of the second week. The timing and magnitude of PHE volume are associated with hematologic factors. Its clinical significance deserves further study.

Abstract

The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method-Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest.Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema.The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

Abstract

The optimal diagnostic evaluation for spontaneous intracerebral hemorrhage (ICH) remains controversial. In this retrospective study, we assessed the utility of early magnetic resonance imaging (MRI) in ICH diagnosis and management.Eighty-nine (72%) of 123 patients with spontaneous ICH underwent a brain CT and MRI within 30 days of ICH onset. Seventy patients with a mean age of 62 ± 15 years were included. A stroke neurologist and a general neurologist, each blinded to the final diagnosis, independently reviewed the admission data and the initial head CT and then assigned a presumed ICH cause under 1 of 9 categories. ICH cause was potentially modified after subsequent MRI review. The final 'gold standard' ICH etiology was determined after review of the complete medical record by an independent investigator. Change in diagnostic category and confidence and the potential impact on patient management were systematically recorded.Mean time to MRI was 3 ± 5 days. Final ICH diagnosis was hypertension or cerebral amyloid angiopathy (CAA) in 50% of patients. After MRI review the stroke neurologist changed diagnostic category in 14%, diagnostic confidence in an additional 23% and management in 20%, and the general neurologist did so in 19, 21 and 21% of patients, respectively. MRI yield was highest in ICH secondary to ischemic stroke, CAA, vascular malformations and neoplasms, and did not differ by age, history of hypertension, hematoma location or the presence of intraventricular hemorrhage.The results of this study suggest potential additive clinical benefit of early MRI in patients with spontaneous ICH.

Abstract

Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.Report of three cases.Three young patients (32-, 30-, and 16-years-old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 h after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.